Prion-like proteins drive several diseases of aging, say leading neurology researchers
September 9, 2013
Many of the brain diseases associated with aging, such as Alzheimer’s and Parkinson’s, are caused by specific proteins that misfold and aggregate into harmful seeds — similar to what happens with prions.
These seeds behave very much like the pathogenic agents known as prions, which cause mad cow disease, chronic wasting disease in deer, scrapie in sheep, and Creutzfeldt-Jakob disease in humans, the researchers say.
The hypothesis could unify scientists’ thinking about several neurodegenerative diseases and suggest therapeutic strategies to combat them.
Walker is research professor at Yerkes National Primate Research Center, Emory University. Jucker is head of the Department of Cellular Neurology at the Hertie Institute for Clinical Brain Research at the University of Tübingen and the German Center for Neurodegenerative Diseases.
Unlike prion diseases, which can be infectious, Alzheimer’s, Parkinson’s, and other neurodegenerative diseases cannot be passed from person to person under normal circumstances. Once all of these diseases take hold in the brain, however, it is increasingly apparent that the clumps of misfolded proteins spread throughout the nervous system and disrupt its function, the researchers suggest.
The two authors of the recent Nature paper where this hypothesis has been proposed were previously the first to show that amyloid-beta, a protein involved in Alzheimer’s disease, forms prion-like seeds that stimulate the aggregation of other amyloid-beta molecules in senile plaques and in brain blood vessels. Since then, a growing number of laboratories worldwide have discovered that proteins linked to other neurodegenerative disorders also share key features with prions.
Age-related neurodegenerative disorders remain stubbornly resistant to the discovery of effective treatments. But Jucker and Walker propose that the concept of pathogenic protein seeding could focus research strategies for these seemingly unrelated diseases.
They also say the concept suggests that therapeutic approaches designed to thwart prion-like seeds early in the disease process could eventually delay or even prevent the diseases.